Richard Lehman’s journal review—7 January 2012

Richard LehmanJAMA  2 Jan 2013  Vol 309
41    There was an issue of JAMA that appeared on December 26th, but it contained nothing really worth disturbing your Christmastide slumbers. The New Year, however, sees JAMA springing into life with lots to interest most doctors. Many of us have delivered babies in our time—and I even have a certificate from the Royal College of Obstetricians and Gynaecologists to prove my competence (hah!)—but we are mostly just bystanders in the great lottery of birth and perinatal outcomes. We have little idea why some babies are born far too early, and whether trying to delay labour using tocolytics has any benefit. The APOSTEL trial randomized 406 Dutch women who were threatened with early labour to either expectant management or nifedipine using slow release tablets. There was absolutely no difference in prolongation of pregnancy and no significant difference in perinatal outcomes.

48    I remarked a few weeks ago that judging from the Nordic crime series that we watch on the television, most people in those parts suffer from seasonal affective disorder all the year round. So I’m surprised to see that among over a million and a half births in Denmark, Sweden, Finland, Norway and Iceland between 1996 and 2007, only 1.8% were to mothers taking serotonin reuptake inhibitors. The risk of stillbirth, neonatal mortality or postneonatal mortality was no different in these pregnancies than the rest.

55    Now back to the vexed question of implantable cardioverter-defibrillators for systolic heart failure. Two trials—MADITT-2 and SCD-HeFT—selected patients with a reduced ejection fraction and randomized them to receive ICDs or medical therapy. Both trials showed an absolute reduction in mortality of about 5-7%. This sophisticated study from Yale seeks to determine from ICD registries whether similar patients in real life get the same benefit. The problem here, of course, is that you cannot identify a matched comparison group in the community who were denied ICDs. So after much hard work and statistical legerdemain, the study shows that the mortality of real-life heart failure patients after ICD implantation for primary prevention is the same as that in the trials, and less than that of the control patients in the trials. Which I guess is a useful thing to know.

71   Armed with this wonderful systematic review of the association between body mass index and all-cause mortality, I shall make a New Year’s resolution to attain a BMI in the mid-range between 30 and 35 by the time I am 65. This will reduce my hazard ratio for death to 0.87 compared with people of “normal” weight (BMI 20-25). Not that one should really be too worried about death at my age: the main thing is to enjoy the remainder of life. As I love eating, I shall have fun striving to attain the appropriate trouser size, tempered by a modicum of exercise. And I shall visit Peru, where they say the food and the exercise are both excellent, though I am not so sure about the trousers.

NEJM  27 Dec 2012  Vol 367
The Yuletide issue of the New England Journal was a pretty dull affair too, dominated worthily by three negative trials. In Bolivia and Ecuador, investigators collected 324 people with severe traumatic brain injury and randomized them to receive treatment based on intracranial pressure monitoring or on whatever forms of non-invasive imaging the clinicians decided on. There was no difference in outcomes. In the massive EVOLVE international trial, Amgen tried out its calcimimetic agent cinacalcet on patients receiving renal dialysis, to see if reducing hyperparathyroidism might improve cardiac outcomes. It performed no better than placebo. And in a big trial of intensive versus less intensive use of CPAPP and oxygen in very premature babies, both groups did equally badly in terms of death and neurodevelopmental damage.

But although more clearly did not mean better in these studies, the editorial, A Glimpse of the Next 100 Years of Medicine, celebrates the coming age when we will know absolutely everything about everybody and be able to treat them accordingly. I shall be long dead before that happens, and my wish for those who survive me is that they will be able to get access to good basic medical care delivered by kind and knowledgeable people who treat them as equals. If they wish to walk around with continuous monitors and be fed tailored drugs to prolong their lives to an average beyond 80 years then that’s up to them.

NEJM  3 Jan 2013  Vol 368
11    For six years in one hospital in Barcelona, patients with acute upper gastrointestinal bleeding were randomised to get a blood transfusion either when their haemoglobin dropped to 9 G/decilitre or 7. In this case less was better: outcomes including bleeding and death were actually improved by a restrictive transfusion strategy.

22    Here’s a study which would have delighted Benjamin Rush, the American Founding Father who loved to use “heroic bleeding” as his main therapy. Italian patients with polycythaemia vera were bled down to a haematocrit of less than 45% as opposed to less than 50%, and proved all the better for it. The difference was in fact quite startling: four times more cardiovascular deaths and thrombotic events in those who maintained a higher haematocrit. Fetch me my basin and my lancet, Adams.

34   Here is an open-label, short-term trial with just 10 patients in each arm, and the conclusion states that “Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection. (Funded by Pharmasset and Gilead Sciences.)” The next paper reports an equally small, equally preliminary trial of two Abbott drugs for HCV which don’t yet have names. I am no expert on hepatitis C, and what is more, neither are you, dear Reader: and I am not reporting these papers in the slightest belief that they will improve your ability to treat patients. They may, however, increase your puzzlement as to how industry-funded studies get selected for inclusion in the NEJM and whether this has anything to do with income from the sale of reprints to pharmaceutical companies.

54    Disease Eradication: now that’s an idea I can sign up to. Will it involve investing trillions of dollars in genomics and biomedicine and tailored new pharmaceuticals? No: it just involves a lot of hard, courageous personal effort by thousands of people using cheap interventions that already exist. Remember the polio vaccinators just murdered in Pakistan: they are the true heroes of medicine. This article goes through a few of the other disease targets, with the odd omission of measles. The amount of global progress is both heartening and disheartening: so much great work being done, but so much more that could have been done and still needs doing. Meanwhile, most of the prestige funding goes into Western boy-scientist dreamland.

Lancet   5 Jan 2013  Vol 381
29    Setting up a good interventional trial in acute heart failure is quite a challenge, and I am quite impressed by this one. I don’t think that by itself it changes practice in any way, but it does show that recombinant human relaxin 2, serelaxin, is an interesting new treatment that deserves further study in heart failure. Decompensated heart failure is the commonest cause for hospital admission, so it was quite unnecessary for Novartis to conduct this trial in 96 centres across 11 countries. But that said, they did recruit 1161 real life elderly patients without regard to systolic ejection fraction: the only atypical entry criterion was a systolic blood pressure above 125 mm Hg after an initial dose of 40mg IV furosemide. All patients received whatever additional treatment their physicians thought necessary, and half of them received an infusion of serelaxin. Those in the latter group were given fewer additional drugs and experienced slightly greater relief of dyspnoea, and more of them were alive at 180 days, though equal numbers ended up back in hospital. If this is a subject that interests you, there is an outstanding editorial by Marvin Konstam to bring you up to speed.

47    One of the great therapeutic innovations during my time as a doctor is the falls clinic. Droves of elderly patients now shuffle through the clinic doors to be assessed by a nurse and sometimes a doctor, and are subjected to varying degrees of diagnostic work-up.  A long letter is then sent instructing us to change all the drugs we have carefully titrated over the preceding year. This Canadian study starts from the premise that we don’t actually know what the commonest causes of falls are, and uses video analysis in two nursing homes to find out. Incorrect shifting of bodyweight is the most frequent, followed by trips, stumbles, and collisions. Slipping was the least frequent cause, at 3%. Medical conditions other than Alzheimer’s showed no association with falling. “This study provides long-missing objective evidence of the cause and circumstances of falls in elderly adults,” say the authors with justifiable pride. A great study.

63   A very worthwhile review of polymyalgia rheumatica rewards those who can get access to full copy of the Lancet. It sheds little light on the aetiology of this common condition—we simply don’t know what causes it—but there is a useful table of the differential diagnoses and the characteristic features. Start with no more than 20mg of prednisolone and taper gently from about a month into treatment: expect a relapse rate of about 50%.

BMJ  5 Jan 2013  Vol 346
Zzz—zaleplon, zolpidem, and zopiclone have become our most popular sleeping pills because they are cheap and they are not benzodiazepines. Not that they differ in any significant way from benzodiazepines, but a lot of doctors have a rooted aversion to prescribing anything ending in azepam. This meta-analysis shows that the Z drugs have small but measurable effects, half of which are pharmacological and half placebo.

We tend to think that heritable factors only govern the risk of cancer in younger age groups. This study shows that is not really the case: although the early cancer risk is the most obvious and the most clinically significant, family history affects cancer incidence right up to the tenth decade of life.

Bipolar disorder is a rare island of reality amidst the diagnostic confusion of psychiatry, and this is a review of rare quality and comprehensiveness. Well, actually, not that rare, in comparison to other BMJ clinical reviews, which are almost all of top quality. Here you have everything you need to know, and the questions you need to ask in consultations. Keep it handy.

Ann Intern Med  1 Jan 2013  Vol 158
27   Last year, while at Yale, I had the opportunity to look through all the writings of Avedis Donabedian, and I also met the great Jack Wennberg who sent me a collection of his early papers. Between them, I think these two outstanding minds have explored the whole conceptual territory of the association between healthcare quality and cost. And yet America blunders ever deeper into overspending and inequality in the provision of healthcare, and our own government is determined to throw the NHS to the mercies of the market. Here is a systematic review of the literature on cost and quality since 1990. It says nothing, as far as I can see, that had not been said better and earlier by Donabedian and Wennberg. When I met the latter at Dartmouth in October, he leaned over to me and said, “Do you think our health system can be fixed?” When I hesitated, he added “I don’t.”

Plant of the Week: Euphorbia “Emmer Green

Our winter garden, like most people’s, is a muddy mess. I’ve even been out in the mild weather to prune the roses and trim dead foliage off the perennials, but it still looks a mess. Yet nestling at the foot of a south facing wall at the front of the house, there is a plant of incontestable star quality: this magnificent euphorbia, flourishing despite the tiny quantity of chlorophyll in its abundant leaves.

It is named after a suburb of Reading, which is quite wrong. This gay and raffish creature of milk white streaked with green is far too much the wild aristocrat for those well-mannered roads, with their set-back red brick houses and tended cars. In the real Emmer Green at this time of the year you are more likely to see neat rows of ornamental cabbages interspersed with pansies.

I have no idea what its needs are, but it seems well content to grow on limy builder’s rubble with us, and it has had no attention over the years but a trim of its dead flower stalks in the autumn. It isn’t easy to find, but get it if you can.